Yang Li, Cui Ming, Zhang Liang, Song Lei
Department of Intensive Care Unit, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027, Liaoning, China.
Department of Emergency, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027, Liaoning, China.
Oncotarget. 2017 Jul 15;8(40):68180-68190. doi: 10.18632/oncotarget.19254. eCollection 2017 Sep 15.
Forkhead box M1 (FOXM1) has been reported as a vital transcription factor in different human malignancies. To date, the mechanisms of FOXM1 in modulating the invasion and metastasis of gastric cancer cells have not been elucidated. In the present study, we found that overexpression of FOXM1 prompted cell migration and invasion of gastric cancer, and increased the expression of Cathepsin D (Cath-D). However, FOXM1 siRNA repressed cell migration and invasion, and also decreased the expression of Cath-D in gastric cancer cells. Blocking of Cath-D repressed FOXM1 overexpression-mediated cell migration and invasion. Mechanically, FOXM1 facilitated the activation of Cath-D promoter. Furthermore, overexpression of Cath-D affected the expression of E-cadherin, leading to epithelial-mesenchymal transition (EMT) of gastric cancer cells. In conclusion, this study demonstrated that FOXM1 promotes gastric cancer cell migration and invasion through inducing expression of Cath-D in gastric cancer. Thus, FOXM1 may be recommended as a potential therapeutic target for gastric cancer patients.
叉头框M1(FOXM1)已被报道为不同人类恶性肿瘤中的一种重要转录因子。迄今为止,FOXM1调节胃癌细胞侵袭和转移的机制尚未阐明。在本研究中,我们发现FOXM1的过表达促进了胃癌细胞的迁移和侵袭,并增加了组织蛋白酶D(Cath-D)的表达。然而,FOXM1 siRNA抑制了胃癌细胞的迁移和侵袭,也降低了Cath-D的表达。阻断Cath-D可抑制FOXM1过表达介导的细胞迁移和侵袭。从机制上讲,FOXM1促进了Cath-D启动子的激活。此外,Cath-D的过表达影响了E-钙黏蛋白的表达,导致胃癌细胞发生上皮-间质转化(EMT)。总之,本研究表明FOXM1通过诱导胃癌中Cath-D的表达促进胃癌细胞的迁移和侵袭。因此,FOXM1可能被推荐作为胃癌患者的潜在治疗靶点。